crossing96/oncoscreening huggingface dataset:
Association of rs8444 polymorphism in the LASS2 3'-UTR and bladder cancer risk in Chinese population.	The aim of the present study was to explore the correlations between single nucleotide polymorphisms in LASS2 gene 3'-untranslated regions and bladder cancer risk in Chinese population. We first performed PCR and sequence for LASS2-3'-UTR in 105 bladder cancer patients and 100 control subjects. Next, multivariate logistic regression analysis was used to determine the relationship between single nucleotide polymorphisms frequency and susceptibility of bladder cancer, and clinical features in 105 cases. In addition, survival curves and Cox Regression analysis were used to investigate the effect of single nucleotide polymorphisms on clinical outcome in 58 cases. Finally, quantitative reverse-transcription PCR and immunohistochemical were performed to explore the influence of single nucleotide polymorphisms on LASS2 expression. We found that a single nucleotide polymorphism (rs8444 C>T) located in the 3'-UTR of LASS2 was significantly associated with the risk of bladder cancer. We also showed the frequency of rs8444 T genotype was higher in bladder cancer group and correlated with the risk of clinical prognosis. Yet, there were no significant correlations between T/C allele frequencies and the distributions of rs8444 genotype and tumor-node-metastasis stage, histological grade and distant metastasis in bladder cancer. Furthermore, we demonstrated that rs8444 C>T could affect LASS2 expression by single nucleotide polymorphism-related mRNA stability. Our results showed that LASS2-3'-UTR rs8444 C>T polymorphism was significantly associated with the individual risk and the poor overall survival of bladder cancer, suggesting that rs8444 TT genotype maybe act as an independent risk factor of susceptibility and clinical prognosis for bladder cancer in Chinese population.	bladder
Inhibition of autophagy enhances the anticancer effect of enzalutamide on bladder cancer.	BACKGROUND: Emerging preclinical evidence suggests a critical role for androgen-mediated androgen receptor (AR) signaling in bladder cancer progression. However, researchers have not determined whether autophagy modulates the efficacy of an enzalutamide (ENZ) treatment in subjects with advanced bladder cancer. In this study, we investigated the synergistic effect of ENZ and autophagy inhibitors on bladder cancer. METHODS: ENZ was used as an anti-AR drug, and chloroquine (CQ), 3-methyladenine (3-MA), and bafilomycin A1 (BAF) were used as autophagy inhibitors. J82, T24, and UMUC3 cell lines were used as models of bladder cancer. A bifluorescence autophagy system with the mRFP-GFP-LC3 plasmid was used to evaluate autophagy flux. Protein and mRNA levels were detected using Western blotting and qPCR, respectively. A Cell Counting Kit-8 (CCK-8) assay, colony assay, and flow cytometry analysis were used to evaluate cell proliferation and apoptosis. Four-week-old BALB/c athymic nude mice were used in the in vivo assay. RESULTS: Based on the results obtained using the bifluorescence autophagy system, ENZ (10-20 μM) significantly facilitated the accumulation of autophagosomes and autolysosomes in the cytoplasm of J82 and T24 cells. Additionally, ENZ significantly increased the expression of autophagy-related genes (AMP-dependent protein kinase (AMPK), autophagy-related gene 5 (ATG5), microtubule-associated protein light chain 3B (LC3B), and UNC-51-like kinase 1 (ULK1)) and proteins (microtubule-associated protein 1 light chain 3-II/I (LC3-II/I), ATG5, and phosphorylated AMP-dependent protein kinase α (p-AMPKα)). The administration of ENZ monotherapy (10-20 μM) to J82 and T24 cells failed to alter proliferation and apoptosis. Concurrent treatment with ENZ and autophagy inhibitors distinctly triggered apoptosis and inhibited proliferation. Genetic inhibition of autophagy by specifically blocking ATG5 with siRNA also increased ENZ-induced apoptosis in J82 and T24 cells. In vivo, concurrent treatment with ENZ (25 mg/kg/day) and CQ (10 mg/kg/day) improved the therapeutic sensitivity by decreasing tumor growth and apoptosis. Additionally, overexpression of AR suppressed ENZ-induced autophagy-related genes (LC3-II/I, ATG5, and p-AMPKα) in T24 cells, and CQ exerted synergistic effects with ENZ to suppressed AR-responsive genes expression (KLK2 and KLK3) in bladder cancer. In UMUC3 cells, ENZ monotherapy directly induced anticancer effects, and concurrent treatment with ENZ and CQ also had a synergistic effect on proliferation and apoptosis. CONCLUSIONS: Autophagy may be a potential mechanism underlying ENZ-resistant bladder cancer. Blockade of autophagy significantly increased ENZ-induced apoptosis in bladder cancer. Thus, concurrent treatment with autophagy inhibitors and ENZ may be a novel therapeutic strategy for bladder cancer.	bladder
Weighted gene coexpression network analysis identifies a new biomarker of CENPF for prediction disease prognosis and progression in nonmuscle invasive bladder cancer.	BACKGROUND: The dreadful prognosis of nonmuscle invasive bladder cancer mainly results from the delay in recognition of individuals with a high risk of progression. Thus, the emphasis of this work lies in developing valuable biomarkers that is conducive to accurately predicting the progression of NMIBC. METHODS: Microarray data from GSE32894 including 209 NMIBC samples were performed by weighted gene coexpression network analysis (WGCNA), which could find modules of highly correlated genes and relate modules to external sample traits. Besides, we constructed a protein-protein interaction to facilitate screening the hub gene. At last, we used RNA-seq and microarray data and clinical information from ArrayExpress (E-MTAB-4321) and GSE13507 to select and validate the candidate gene. RESULTS: In current paper, blue module of 13 gene coexpression clusters we identified was selected as the key modules. Seven genes namely: CDCA8, CENPF, MCM6, MELK, PRC1, STIL, and TPX2 have been identified as candidate genes. Notably, among them, only elevated CENPF in NIMBC tissue was closely associated with low progression-free survival (PFS) and overall survival (OS) rate in three datasets and had a large area under receiver operating characteristic (ROC) curve. Finally, CENPF was identified as an effective biomarker in NMIBC. CONCLUSION: Therefore, our findings submit a new progressive and prognostic molecular marker and therapeutic target for NMIBC. Moreover, these genes that deserve to be further researched may improve the comprehension about the occurrence and development of superficial bladder cancer.	bladder
[Recurrent invasive bladder urothelial carcinoma treated by cystectomy with substitutive ileal enterocystoplasty: case report].	We here report a case of bladder urothelial carcinoma, a rare tumor in subjects less than 40 years, as well as our therapeutic experience. The study involved a 37-year old patient with a history of urinary tract infection and of staying at a riparian area (bilharzia) presenting with hypogastralgia and total macroscopic hematuria. Clinical and paraclinical assessment showed voluminous bladder mass suggesting infiltrative tumor without local or distant lymph node or organic involvement. Surgical management was based on resection of bladder tumor and biopsy followed by total cystectomy with substitutive ileal enterocystoplasty. The postoperative course was uneventful. The patient also underwent adjuvant chemotherapy and vitamin B-12 therapy. Clinical and paraclinical assessment, performed after 6 and 12 months, showed no recurrence.	bladder
A Consensus Molecular Classification of Muscle-invasive Bladder Cancer.	BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. OBJECTIVE: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. DESIGN, SETTING, AND PARTICIPANTS: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models. RESULTS AND LIMITATIONS: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment. CONCLUSIONS: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials. PATIENT SUMMARY: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.	bladder
Quality Indicators for Bladder Cancer Services: A Collaborative Review.	CONTEXT: There is a lack of accepted consensus on what should constitute appropriate quality-of-care indicators for bladder cancer. OBJECTIVE: To evaluate the optimal management of bladder cancer and propose quality indicators (QIs). EVIDENCE ACQUISITION: A systematic review was performed to identify literature on current optimal management and potential quality indicators for both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer. A panel of experts was convened to select a recommended list of QIs. EVIDENCE SYNTHESIS: For NMIBC, preoperative QIs include tobacco cessation counselling and appropriate imaging before initial transurethral resection of bladder tumour (TURBT). Intraoperative QIs include administration of antibiotics, proper safe conduct of TURBT using a checklist, and performing restaging TURBT with biopsy of the prostatic urethra in appropriate cases. Postoperative QIs include appropriate receipt of perioperative adjuvant therapy, risk-stratified surveillance, and appropriate decision to change therapy when indicated (eg, bacillus Calmette-Guerin [BCG] unresponsive). For MIBC, preoperative QIs include multidisciplinary care, selection for candidates for continent urinary diversion, receipt of neoadjuvant cisplatin-based chemotherapy, time to commencing radical treatment, consideration of trimodal therapy as a bladder-sparing alternative in select patients, preoperative counselling with stoma marking, surgical volume of radical cystectomy, and enhanced recovery after surgery protocols. Intraoperative QIs include adequacy of lymphadenectomy, blood loss, and operative time. Postoperative QIs include prospective standardised monitoring of morbidity and mortality, negative surgical margins for pT2 disease, appropriate surveillance after primary treatment, and adjuvant cisplatin-based chemotherapy in appropriate cases. Participation in clinical trials was highlighted as an important component indicating high quality of care. CONCLUSIONS: We propose a set of QIs for both NMIBC and MIBC based on established clinical guidelines and the available literature. Although there is currently a lack of level 1 evidence for the benefit of implementing these QIs, we believe that the measurement of these QIs could aid in the improvement and benchmarking of optimal care for bladder cancer. PATIENT SUMMARY: After a systematic review of existing guidelines and literature, a panel of experts has recommended a set of quality indicators that can help providers and patients measure and strive towards optimal outcomes for bladder cancer care.	bladder
The effect of radical cystectomy on survival in patients with metastatic urothelial carcinoma of the urinary bladder.	BACKGROUND: To test the effect of radical cystectomy (RC) with chemotherapy vs only chemotherapy on overall mortality (OM) in metastatic urothelial carcinoma of the urinary bladder (mUCUB). METHODS: Within the Surveillance, Epidemiology, and End Results registry (2004-2016), we identified patients with mUCUB. Stratification was made according to treatment: RC with chemotherapy vs only chemotherapy. Kaplan-Meier plots and multivariable Cox regression models were used before and after 1:1 propensity score (PS) matching and inverse probability of treatment weighting (IPTW). RESULTS: Of 2414 patients with mUCUB, 500 (21.0%) vs 1914 (79.0%) were treated with RC with chemotherapy vs only chemotherapy, respectively. In multivariable Cox regression models, RC with chemotherapy was associated with lower OM in the overall cohort (hazard ratio [HR], 0.5; P < .001), after 1:1 PS matching (HR, 0.5; P < .001), after IPTW (HR, 0.5; P < .001) and after accounting for number and location of metastases (HR, 0.5; P < .001). However, higher overall survival after RC with chemotherapy was only observed in patients with one metastatic site (21 vs 16 months; P = .001). CONCLUSION: In contemporary patients with mUCUB, RC with chemotherapy is associated with lower OM rates, relative to chemotherapy alone, but only in patients with a single metastatic site. These individuals accounted for the vast majority of patients in whom an RC was performed, despite the presence of metastatic disease.	bladder
Environment and urinary bladder cancer. A historical perspective.	Our understanding of aetiological factors associated with urinary bladder cancer has radically improved over the last decades. Cigarette smoking is considered the most important risk factor, even in the industrialised world, while various occupational and environmental exposures to chemicals are also held responsible. The link between bladder cancer and schistosomiasis, highly prevalent in sub-Saharan Africa, Sudan, Egypt, and Yemen, provides input for investigating and potentially preventing bladder carcinogenesis. Growing concern regarding environmental diseases prompts investigation into the historical milestones that have helped disentangle the relationships between health and environment.	bladder
Prediction of complication related death after radical cystectomy for bladder cancer with machine learning methodology.	Purpose: To create a pre-operatively usable tool to identify patients at high risk of early death (within 90 days post-operatively) after radical cystectomy and to assess potential risk factors for post-operative and surgery related mortality.Materials and methods: Material consists of 1099 consecutive radical cystectomy (RC) patients operated at 16 different hospitals in Finland 2005-2014. Machine learning methodology was utilized. For model building and testing, the data was randomly divided into training data (n = 733, 66.7%) and independent testing data (n = 366, 33.3%). To predict the risk of early death after RC from baseline variables, a binary classifier was constructed using logistic regression with lasso regularization. Finally, a user-friendly risk table was constructed for practical use.Results: The model resulted in an area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI = 0.59-0.87). The strongest risk factors were: American Society of Anesthesiologists physical status classification (ASA), congestive heart failure (CHF), age adjusted Charlson comorbidity index (ACCI) and chronic pulmonary disease.Conclusion: This study with a novel methodological approach adds CHF and chronic pulmonary disease to previously known independent prognostic risk factors for early death after RC. Importantly, the risk prediction tool uses purely pre-operative data and can be used before surgery.	bladder
Lymph Node Dissection for Advanced Bladder Cancer: Is There a Role?	The role of a thorough pelvic lymph node dissection at radical cystectomy for high risk bladder cancer is an important component for quality surgical care. Selected patients with advanced disease involving the retroperitoneal lymph nodes (limited nodal disease, significant response to systemic therapy, and the ability to resect all sites of prior involvement) may benefit from surgical resection.	bladder
Association Between FDA Label Restriction and Immunotherapy and Chemotherapy Use in Bladder Cancer.	This research letter discusses the association between label restrictions by the US Food and Drug Administration on first-line immunotherapy for advanced bladder cancer and subsequent changes in practice.	bladder
The Role of Fluorescence In Situ Hybridization for Predicting Recurrence after Adjuvant bacillus Calmette-Guérin in Patients with Intermediate and High Risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data.	PURPOSE: The objective of this study was to assess the value of fluorescence in situ hybridization to predict early recurrence in patients with nonmuscle invasive bladder cancer at intermediate and high risk treated with bacillus Calmette-Guérin. MATERIALS AND METHODS: We performed a systematic review using MEDLINE®, Embase® and the Cochrane Library. Individual patient data from prospective observational studies of fluorescence in situ hybridization in patients treated with bacillus Calmette-Guérin were included. A 2-stage individual patient data meta-analysis was done to assess the value of fluorescence in situ hybridization to predict tumor recurrence after bacillus Calmette-Guérin induction therapy. RESULTS: From a total of 4 studies we obtained individual data on 422 patients, of whom 408 with a median followup of 18.8 months were included in the final analysis. When fluorescence in situ hybridization was positive, the recurrence HR was 1.20 (95% CI 0.81-1.79) before bacillus Calmette-Guérin (time 0), 2.23 (95% CI 1.31-3.62) at 6 weeks (time 1), 3.70 (95% CI 2.34-5.83) at 3 months (time 2) and 23.44 (95% CI 5.26-104.49) at 6 months (time 3). CONCLUSIONS: A positive fluorescence in situ hybridization test after bacillus Calmette-Guérin correlated with higher risk of recurrent tumor. Fluorescence in situ hybridization could aid urologists in risk stratifying and counseling patients. Based on the HR and the narrowest CI the preferred timing of fluorescence in situ hybridization is 3 months after transurethral resection of bladder tumor. This is also in time for patients in whom induction therapy fails to enter clinical trials or change the treatment strategy.	bladder
[Status of the availability and use of next generation sequencing (NGS) in bladder cancer-a questionnaire within the uropathology working group].	BACKGROUND: Technical advancement and availability of high-throughput analysis has advanced molecular subtyping of most cancers. Thus, new possibilities for precision oncology have emerged. AIM: Therefore, we aimed to collect data regarding availability and use of next generation sequencing (NGS) for urothelial cancer within the uropathology working group of the German Society of Pathology. METHODS: We collected data by questionnaires and additionally asked for sequencing results of bladder cancers in the participating institutions. RESULTS: A total of 13 university-affiliated institutes of pathology took part in the survey. All university institutes offer NGS-based molecular panel diagnostics and provide panels covering between 15 and 170 genes. Altogether, only 20 bladder cancers were sequenced in routine diagnostics and for 10 cancers potential targeted treatment options were available. DISCUSSION: So far, despite availability of NGS diagnostics at university institutes of pathology, only few bladder cancer samples have been sequenced. Based on current data from the molecular subtyping of bladder cancers, we recommend a step-by-step protocol with basic immunohistochemistry analysis and subsequent subtype-dependent analyses, e.g., alterations of the fibroblast growth factor receptors (FGFR) or comprehensive gene panel analyses.	bladder
Minimally invasive vs open radical cystectomy in patients with bladder cancer: A systematic review and meta-analysis of randomized controlled trials.	OBJECTIVE: Minimally invasive surgical (MIS) approaches to radical cystectomy (RC) develop well in the past decades. We performed the present study to compare the perioperative outcomes, pathological outcomes, and oncologic outcomes between MIS approaches and open radical cystectomy (ORC) for bladder cancer. METHOD: We conducted a comprehensive study search up to March 2019, searching the online database Embase, PubMed and Cochrane Library. RESULTS: A total of 8 randomized controlled trials comprising 805 patients were included. We observed that MIS approaches were significantly associated with lower estimated blood loss (WMD = -343.21; 95%CI -431.34 to -255.08; P < 0.001), shorter length of stay (WMD = -0.76; 95%CI -1.28 to -0.24; P = 0.004), shorter time to flatus and diet (WMD = -0.46; 95%CI -0.64 to -0.27; P < 0.001; WMD = -0.92; 95%CI -1.58 to -0.28; P = 0.005; respectively), longer operation time (WMD = 61.38; 95%CI 34.89 to 87.88; P < 0.001), fewer 30-day overall complication (OR = 0.36; 95%CI 0.17 to 0.75; P = 0.007). And we did not detect significant difference in terms of 30-day (P = 0.278) and 90-day major complication (P = 0.899), positive surgical margins (P = 0.986), lymph node yield (P = 0.711), OS (P = 0.473), CSS (P = 0.778), RFS (P = 0.880), PFS (P = 0.324) between MIS approaches and ORC. CONCLUSION: In the present studies, we demonstrated that MIS approaches improved perioperative outcomes and had similar pathological and oncological outcomes compared with ORC. Stratified by type of MIS approaches, the results are similar. In conclusion, MIS approaches could serve as an alternative choice in patients with bladder cancer. However, long-term clinical outcomes highlight the need for future studies.	bladder
Does Health Insurance Modify the Association Between Race and Cancer-Specific Survival in Patients with Urinary Bladder Malignancy in the U.S.?	Background: Scientific evidence on the effect of health insurance on racial disparities in urinary bladder cancer patients' survival is scant. The objective of our study was to determine whether insurance status modifies the association between race and bladder cancer specific survival during 2007-2015. Methods: The 2015 database of the cancer surveillance program of the National Cancer Institute (n = 39,587) was used. The independent variable was race (White, Black and Asian Pacific Islanders (API)), the main outcome was cancer specific survival. Health insurance was divided into uninsured, any Medicaid and insured. An adjusted model with an interaction term for race and insurance status was computed. Unadjusted and adjusted Cox regression analysis were applied. Results: Health insurance was a statistically significant effect modifier of the association between race and survival. Whereas, API had a lower hazard of death among the patients with Medicaid insurance (HR 0.67; 95% CI 0.48-0.94 compared with White patients, no differences in survival was found between Black and White urinary bladder carcinoma patients (HR 1.24; 95% CI 0.95-1.61). This may be due a lack of power. Among the insured study participants, Blacks were 1.46 times more likely than Whites to die of bladder cancer during the 5-year follow-up (95% CI 1.30-1.64). Conclusions: While race is accepted as a poor prognostic factor in the mortality from bladder cancer, insurance status can help to explain some of the survival differences across races.	bladder